Iron Deficiency Anemia, B-Thalassemia Minor, and Anemia of Chronic Disease
Iron Deficiency Anemia, B-Thalassemia Minor, and Anemia of Chronic Disease
We observed increased numbers of an infrequently referenced poikilocyte, the prekeratocyte, in iron deficiency anemia (IDA) compared with β-thalassemia minor and anemia of chronic disease (ACD) and, therefore, chose to quantify these cells and other morphologic features in these anemias. Prekeratocytes were observed in 31 (78%) of 40 IDAs vs 11 (37%) of 30 β-thalassemias (P = .001) and 5 (13%) of 40 ACDs (P < .001) and averaged 0.78 per 1,000 RBCs in IDA vs 0.21 in β-thalassemia (P < .001) and 0.075 in ACD (P < .001). Pencil cells also were more commonly seen and more numerous in IDAs than in β-thalassemia or ACD. Target cells were present in most IDAs and thalassemia and in similar numbers. Basophilic stippling was seen in only 5 (17%) of the β-thalassemias. Our results lend quantitative support to prekeratocytes and pencil cells as morphologic features favoring the diagnosis of IDA but fail to support the diagnostic usefulness of target cells and basophilic stippling in discriminating IDA and β-thalassemia minor.
The peripheral blood morphologic findings in various types of anemias are the subject of abundant anecdotal description but few supportive quantitative data. This limits the application of morphologic data to differential diagnosis. A commonly encountered differential is that of microcytic anemia, which, for practical purposes, is limited to iron deficiency anemia (IDA), thalassemia, and a minority of cases of anemia of chronic disease (ACD). Morphologic features commonly cited as favoring one diagnosis over the others include the presence of pencil cells in IDA and target cells and basophilic stippling in β-thalassemia minor.
In addition to these classic morphologic findings, we have observed in smears of IDA increased numbers of rarely described poikilocytes known as prekeratocytes. These are characterized by distinct, sharp-edged, submembranous vacuoles and intact central pallor Figure 1. They were originally described by Bell as precursor forms in the sequence of spiculated red cell (burr cell) formation. Prekeratocytes are observed in microangiopathic hemolytic anemias and, as the name implies, may give rise to keratocytes, a poikilocyte morphologically similar to the helmet cell. They have often been inappropriately referred to as "blister cells." True blister cells, described in sickle cell disease, show compartmentalization of their hemoglobin to one side, the remainder of the cell outlined by a thin, hemoglobin-free membrane (Figure 1, inset). Although these cells are similar to the "eccentrocytes" or "ghost cells" of severe oxidant hemolysis, they are readily identified by context.
(Enlarge Image)
Figure 1.
Prekeratocyte (arrow) and pencil cell (arrowhead) in iron deficiency anemia (Wright-Giemsa, ×1,000). Inset, Blister cell in sickle cell disease (Wright-Giemsa, ×1,000).
Because of the lack of quantitative data supporting classic morphologic descriptions of the microcytic anemias, we endeavored to test the discriminatory power of prekeratocytes and other morphologic features in the differential diagnosis of IDA, β-thalassemia minor, and ACD.
Abstract and Introduction
Abstract
We observed increased numbers of an infrequently referenced poikilocyte, the prekeratocyte, in iron deficiency anemia (IDA) compared with β-thalassemia minor and anemia of chronic disease (ACD) and, therefore, chose to quantify these cells and other morphologic features in these anemias. Prekeratocytes were observed in 31 (78%) of 40 IDAs vs 11 (37%) of 30 β-thalassemias (P = .001) and 5 (13%) of 40 ACDs (P < .001) and averaged 0.78 per 1,000 RBCs in IDA vs 0.21 in β-thalassemia (P < .001) and 0.075 in ACD (P < .001). Pencil cells also were more commonly seen and more numerous in IDAs than in β-thalassemia or ACD. Target cells were present in most IDAs and thalassemia and in similar numbers. Basophilic stippling was seen in only 5 (17%) of the β-thalassemias. Our results lend quantitative support to prekeratocytes and pencil cells as morphologic features favoring the diagnosis of IDA but fail to support the diagnostic usefulness of target cells and basophilic stippling in discriminating IDA and β-thalassemia minor.
Introduction
The peripheral blood morphologic findings in various types of anemias are the subject of abundant anecdotal description but few supportive quantitative data. This limits the application of morphologic data to differential diagnosis. A commonly encountered differential is that of microcytic anemia, which, for practical purposes, is limited to iron deficiency anemia (IDA), thalassemia, and a minority of cases of anemia of chronic disease (ACD). Morphologic features commonly cited as favoring one diagnosis over the others include the presence of pencil cells in IDA and target cells and basophilic stippling in β-thalassemia minor.
In addition to these classic morphologic findings, we have observed in smears of IDA increased numbers of rarely described poikilocytes known as prekeratocytes. These are characterized by distinct, sharp-edged, submembranous vacuoles and intact central pallor Figure 1. They were originally described by Bell as precursor forms in the sequence of spiculated red cell (burr cell) formation. Prekeratocytes are observed in microangiopathic hemolytic anemias and, as the name implies, may give rise to keratocytes, a poikilocyte morphologically similar to the helmet cell. They have often been inappropriately referred to as "blister cells." True blister cells, described in sickle cell disease, show compartmentalization of their hemoglobin to one side, the remainder of the cell outlined by a thin, hemoglobin-free membrane (Figure 1, inset). Although these cells are similar to the "eccentrocytes" or "ghost cells" of severe oxidant hemolysis, they are readily identified by context.
(Enlarge Image)
Figure 1.
Prekeratocyte (arrow) and pencil cell (arrowhead) in iron deficiency anemia (Wright-Giemsa, ×1,000). Inset, Blister cell in sickle cell disease (Wright-Giemsa, ×1,000).
Because of the lack of quantitative data supporting classic morphologic descriptions of the microcytic anemias, we endeavored to test the discriminatory power of prekeratocytes and other morphologic features in the differential diagnosis of IDA, β-thalassemia minor, and ACD.
